A5101844949- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Metabolomics and Mass Spectrometry Studies
- Radiation Therapy and Dosimetry
- Genetic factors in colorectal cancer
- Gut microbiota and health
- Cancer Cells and Metastasis
- Mitochondrial Function and Pathology
- Hematopoietic Stem Cell Transplantation
- Folate and B Vitamins Research
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Cancer, Stress, Anesthesia, and Immune Response
- Amino Acid Enzymes and Metabolism
- Childhood Cancer Survivors' Quality of Life
- Liver physiology and pathology
- Hair Growth and Disorders
- Skin and Cellular Biology Research
- Clinical Nutrition and Gastroenterology
- Dermatological and Skeletal Disorders
- Inflammatory Bowel Disease
- Molecular Biology Techniques and Applications
Michigan Medicine
2023
University of Michigan
2018-2023
Michigan Center for Translational Pathology
2023
Bayer (Germany)
2016-2020
Ann Arbor Center for Independent Living
2020
Laboratoire d’immunologie intégrative du cancer
2018
Technische Universität Berlin
2016
Ovarian cancer is typified by the development of chemotherapy resistance. Chemotherapy resistance associated with high aldehyde dehydrogenase (ALDH) enzymatic activity, increased "stemness," and expression stem cell marker CD133. As such, ALDH activity has been proposed as a therapeutic target. Although it remains controversial which 19 family members drive resistance, ALDH1A have primarily linked resistant stemness. We identified two selective inhibitors (ALDH1Ai). ALDH1Ai preferentially kills CD133
Metabolic flux technology with the Seahorse bioanalyzer has emerged as a standard technique in cellular metabolism studies, allowing for simultaneous kinetic measurements of respiration and glycolysis. Methods to extend utility versatility metabolic assay would undoubtedly have immediate wide-reaching impacts. Herein, we describe platform that couples high-content fluorescence imaging simultaneously provide means normalization data cell number; analyze cycle distribution; quantify...
Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of pancreatic cancer with rising incidence in developing countries and overall 5-year survival rates less than 5%. The frequent mutations PDAC are gain-of-function KRAS as well loss-of-function p53. Both have severe impacts on metabolism tumor cells. Many these metabolic changes mediated by transporters or channels that regulate exchange metabolites ions between intracellular compartment microenvironment. In study...
Abstract Background Metabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway. Methods utilized doxycycline-inducible shRNA-mediated strategy knockdown GOT1 PDA colorectal (CRC) cell lines tumor models similar genotype. These were analyzed for ability form...
Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 mutated more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental studies the contribution individual genes to carcinogenesis. Oncogenic Kras occur early during carcinogenesis and are considered an initiating event. In contrast, p53 later tumor progression. our model, we recapitulated order disease, with mutation following expression...
// Valeria Santoro 1 , * Ilya Kovalenko 2 Kim Vriens 3 4 Stefan Christen Andreas Bernthaler Andrea Haegebarth Sarah-Maria Fendt and Sven Christian Bayer AG, Drug Discovery, Berlin 13353, Germany Current address: University of Michigan, Cancer Center, Ann Arbor, MI 48108, USA Laboratory Cellular Metabolism Metabolic Regulation, VIB Center for Biology, VIB, Leuven 3000, Belgium Department Oncology, KU Institute (LKI), These authors contributed equally to this work Correspondence to: Christian,...
Summary Pancreatic Ductal Adenocarcinoma (PDA) is characterized by abundant infiltration of tumor associated macrophages (TAMs). TAMs have been reported to drive resistance gemcitabine, the front-line chemotherapy in PDA, though mechanism this remains unclear. Profiling metabolite exchange, we demonstrate programmed PDA cells release a spectrum pyrimidine species. These include deoxycytidine, which inhibits gemcitabine through molecular competition at level drug uptake and metabolism....
Abstract Metabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway. Here we tested if type impacted GOT1 dependence comparing PDA colorectal (CRC) cell lines tumor models similar genotype. found CRC be insensitive inhibition, contrasting markedly with PDA, which...
Summary Intestinal epithelial cell (IEC) damage by T cells contributes to alloimmune, autoimmune and iatrogenic diseases such as graft-versus-host disease (GVHD), inflammatory bowel (IBD) immune checkpoint blockade (ICB) mediated colitis, respectively. Despite significant advances in understanding the aberrant biology of these diseases, little is known about how fundamental biological processes target IECs influence severity. Here, through analyses metabolic pathways IECs, we identified...
Abstract The objective of the present study is to identify modulators cellular metabolism among transportome genes which could potentially be exploited as targets in pancreatic ductal adenocarcinoma (PDAC). Indeed cancer cells have ability adapt order survive stressful environment where oxygen and nutrients are limited due poor vasculature outgrowth stromal component. Thus, disrupting mechanisms metabolic adaptation inhibit tumor proliferation or sensitize treatment. Ion channels...
Abstract SLC25A32 is a member of the solute carrier 25 family mitochondrial transporters. transports tetrahydrofolate (THF) as well FAD into mitochondria and regulates one-carbon metabolism redox balance. While it known that cancer cells require FAD-dependent for generation nucleotides, lipids maintenance homeostasis to sustain growth, role in cell survival remains unexplored. Our results indicate gene highly amplified different tumors its amplification correlates with increased mRNA...
Inflammatory breast cancer (IBC) is an extremely aggressive and rare form of that disproportionally affects African American younger women. While IBC represents 1-5% cancers, it accounts for 10% all deaths annually in the United States. We have previously shown metabolic characteristics IBC, specifically triple negative (TN) inflammatory cell line SUM149, are significantly altered from those normal cells. RhoC, a member Ras superfamily GTPases, contributes to metastatic phenotype acts as...
Pancreatic ductal adenocarcinoma (PDA) remains a leading cause of cancer related death, contrasting relatively low incidence rate. A principle barrier in PDA treatment is the physiology tumors, characterized by densely fibrotic stroma, rich with immune cell infiltration including macrophages. Macrophages are polarized environmental cues which dictate their function. In PDA, macrophages within tumor (tumor associated macrophages, or TAMs) strongly immunosuppressive, inhibiting both and...
SUMMARY Metabolic flux technology with the Seahorse bioanalyzer has emerged as a standard technique in cellular metabolism studies, allowing for simultaneous kinetic measurements of respiration and glycolysis. Methods to extend utility versatility metabolic assay would undoubtedly have immediate wide-reaching impacts. Herein, we describe platform that couples high-content fluorescence imaging simultaneously enhance normalization data cell number; analyze cycle progression; quantify...
Abstract The ability to perform concurrent, dynamic measurements of multiple parameters tumor cell health can provide valuable mechanistic insight. For example, a single compound may exhibit cytotoxic and/or cytostatic properties, depending on the type being targeted as well concentration and duration treatment. In addition, evaluating immune-cancer interactions or metabolic exchange between cancer stromal cells be critical component elucidating mechanism action. However, standard methods...